Liver Functions Prt. 2 Flashcards
JAUNDICE
• From the french word____ which means “yellow”
jaune
One of the oldest known pathologic conditions reported & described by Hippocratic physicians
Jaundice
Jaundice
• Yellowish discoloration of the (3).
• Due to the retention of____
• May also occur due to the retention of other substances
skin, eyes and mucous membranes
bilirubin
The normal level of bilirubin is
0.2-1.0 mg/dL
Jaundice will only become overt or noticeable to the naked eye at above____
3.0 mg/dL.
_______- term used in the laboratory to refer to a serum or plasma with a yellowish discoloration due to bilirubin.
• Dark yellow discoloration of serum/plasma
• Yellow serum will stay in the walls of the test tube once tilted
• Will have effects in other test results
Icterus
Total Bilirubin Upper Limit -
1.0 to 1.5 mg/dL
Overt Jaundice - Not noticeable by the naked eye until it reaches
3.0 to 5.0 mg/dL
Normal
Noticeable
TB upper limit
Overt jaundice
0.2-1.0 mg/dL
3.0 mg/dL.
1.0 to 1.5 mg/dL
3.0 to 5.0 mg/dL
Liver function test based upon bile pigment metabolism
licteric index
Icteric serum
[Bilirubin concentration)
1+=
2+ =
3+=
4 =
2.5 mg/dL
5.0 mg/dL
10.0 mg/dL
20.0 mo/dL
TYPES OF JAUNDICE
Pre-Hepatic
Hepatic
Post-Hepatic
• Excessive amount of bilirubin is presented to the liver due to excessive hemolysis.
• Excessive amount of bilirubin is presented to the liver for metabolism
Due to processes/diseases before conjugation in the liver
PRE-HEPATIC JAUNDICE
Elevated unconjugated bilirubin (B1) in serum.
PRE-HEPATIC JAUNDICE
Hemolysis, Hemolytic Anemia, Malaria
Increased breakdown of RBCs
Increased conjugated bilirubin in the blood = unconjugated hyperbilirubinemia
PRE-HEPATIC JAUNDICE
• Impaired cellular uptake, defective conjugation or abnormal secretion by the liver cell (= intrinsic liver defect/diseases)
HEPATIC JAUNDICE
Both conjugated and unconjugated bilirubin may be elevated in serum.
HEPATIC JAUNDICE
- Increased B1
Unconjugated Hyperbilirubinemia
Unconjugated Hyperbilirubinemia (2)
Gilbert Syndrome
Crigler-Najjar Syndrome
Gilbert Syndrome -› Benign autosomal recessive hereditary disorder
Genetic mutation of _____
UGT1A1 = UDP Glucuronosyltransferase
Family 1 Member A1
Gene that encodes the
UDPGT enzyme = can’t
conjugate B1 to B2
UGT1A1
uridine diphosphate glucuronosyltransferase 1A1 gene (UGT1A1)
- Elevated B1
- 30% of the liver is still functional = some conjugation may still be possible
- May have no symptoms but w/ mild icterus
Gilbert Syndrome
- More serious than Gilbert syndrome
Crigler-Najjar Syndrome
Crigler-Najjar Syndrome
Deficiency of _____ enzyme
uridine diphosphate-glucuronosyltransferase (UDPGT)
- Complete absence of UDPGT
Accumulation of bilirubin in the brain = neuronal degeneration = Kernicterus
<1 year life expectancy
Some may reach 1 year = phototherapy
Crigler-Najjar Syndrome Type 1
Severe/partial deficiency of UDPGT = decreased B2
• Px. can still survive w/ phototherapy
Crigler-Najjar Syndrome Type 2
UV rays can oxidize bilirubin to_____
If bilirubin is exposed to light = falsely decreased = must be covered upon testing
biliverdin
- Increased B2
Conjugated Hyperbilirubinemia
Conjugated Hyperbilirubinemia (2)
Dubin-Johnson Syndrome
Rotor’s Syndrome
-› Autosomal recessive disease
• Presents shortly after birth
Increased B2 w/o elevation of liver
enzymes (ALT & AST) = can also
see Delta Bilirubin
Dubin-Johnson Syndrome
Defective excretion of bilirubin by
hepatocytes to bile canal = B2
returns to bloodstream
Deficiency in______
Dubin-Johnson Syndrome
canalicular multidrug resistance/multispecific organic anionic transporter protein (MDR2/cMOAT)
- Liver granules aren’t pigmented = liver biopsy
- Increased B2
• Unknown etiology w/ good prognosis
Rotor’s Syndrome
Same symptoms w/ Dubin-Johnson Syndrome
> Differentiated through liver
biopsy = absence of liver granules
Rotor’s Syndrome
T or F
Physiologic Jaundice of the Newborn - Newborn
Jaundice is normal
True
Physiologic Jaundice of the Newborn
Deficiency of _____= last enzyme to be fully developed = liver isn’t fully developed
UDPGT
- Bilirubin-conjugation inhibition
Lucey-Driscoll Syndrome
Lucey-Driscoll Syndrome
AKA
Transient Familial Neonatal
Hyperbilirubinemia
Circulating inhibitor of bilirubin conjugation
Increase of B1 = can’t be conjugated
Lucey-Driscoll Syndrome
• Impaired bilirubin excretion due to mechanical obstruction to bile flow.
Due to processes/diseases after conjugation in the liver
POST-HEPATIC JAUNDICE
Elevated conjugated bilirubin (B2) in serum.
POST HEPATIC JAUNDICE
Biliary Obstructive Diseases - Gallstones, Tumor
Increased conjugated bilirubin in the blood
Can’t be fully excreted to the
feces/urine = goes back to the
bloodstream
POST HEPATIC JAUNDICE
Slightly increased unconjugated bilirubin = lesser than B2
Duct obstruction = buildup of
pressure = liver injury = impaired
conjugation function
Not all B1 will be converted to B2
POST HEPATIC JAUNDICE
It is most commonly caused by an increased amount of bilirubin being presented to the liver such as that seen in acute and chronic hemolytic anemias.
occurs when the problem causing the jaundice occurs prior to liver metabolism.
Prehepatic jaundice
Other term for pre hepatic jaundice
_______ because the fraction of bilirubin increased in people with prehepatic jaundice is the unconjugated fraction.
unconjugated hyperbilirubinemia
are hepatic causes of jaundice that result in elevations in unconjugated bilirubin.
Gilbert’s disease
Crigler-Najjar syndrome
physiologic jaundice of the newborn
Conditions such as _____ and_____ are hepatic causes of jaundice that result in elevations in conjugated bilirubin.
Dubin-Johnson
Rotor’s syndrome
________, first described in the early twentieth century, is a benign autosomal recessive hereditary disorder that affects approximately 5% of the US population.
Gilbert’s syndrome
Gilbert’s syndrome results from a genetic mutation in the______ gene that produces the enzyme_______ important for bilirubin metabolism.
The UGT1A1 gene is located on chromosome 2, and other mutations of this same gene produce Crigler-Najjar syndrome, a more severe and dangerous form of hyperbilirubinemia.
UGT1A1
uridine diphosphate glucuronosyltransferase
occurs when the problem causing the jaundice occurs prior to liver metabolism.
It is most commonly caused by an increased amount of bilirubin being presented to the liver such as that seen in acute and chronic hemolytic anemias.
Prehepatic jaundice
The liver responds by functioning at maximum capacity; therefore, people with______ rarely have bilirubin levels that exceed 5.0 mg/dL because the liver is capable of handling the overload.
prehepatic jaundice
This type of jaundice may also be referred to as________ because the fraction of bilirubin increased in people with prehepatic jaundice is the unconjugated fraction.
unconjugated hyperbilirubinemia
is not water soluble, is bound to albumin, is not filtered by the kidneys, and is not seen in the urine.
unconjugated bilirubin
Type of jaundice
intrinsic liver defect or disease
Hepatic
Hepatic jaundice
Crigler-Najjar syndrome
Dubin-Johnson syndrome
Gilbert’s disease
neonatal physiologic jaundice of the newborn
(3) are hepatic causes of jaundice that result in elevations in unconjugated bilirubin.
Gilbert’s disease
Crigler-Najjar syndrome
physiologic jaundice of the newborn
Conditions such as _____ and_____ are hepatic causes of jaundice that result in elevations in conjugated bilirubin.
Dubin-Johnson
Rotor’s syndrome
Gilbert’s syndrome results from a genetic mutation in the______ gene that produces the enzyme UDPGT — uridine diphosphate glucuronosyltransferase, one of the enzymes important for bilirubin metabolism.
UGT1A1
The UGT1A1 gene is located on chromosome 2, and other mutations of this same gene produce_______ syndrome, a more severe and dangerous form of hyperbilirubinemia.
Crigler-Najjar syndrome
Of the many causes of jaundice,______ is the most common cause, and interestingly, it carries no morbidity or mortality in the majority of those affected and carries generally no clinical consequences.
It is characterized by intermittent unconjugated hyperbilirubinemia, underlying liver disease due to a defective conjugation system in the absence of hemolysis.
Gilbert’s syndrome
Crigler-Najjar syndrome may be divided into two types:
type 1, where there is a ______ of enzymatic bilirubin conjugation
type II, where there is a______ causing a severe_____ of the enzyme responsible for bilirubin conjugation.
complete absence
mutation; deficiency
Unlike Gilbert’s syndrome,______ is rare and is a more serious disorder that may result in death.
Crigler-Najjar syndrome
Dubin-Johnson syndrome and Rotor’s syndrome are characterized as_______
conjugated hyperbilirubinemias
is a rare autosomal recessive inherited disorder caused by a deficiency of the canalicular multidrug resistance/multispecific organic anionic transporter protein (MDR2/cMOAT).
In other words, the liver’s ability to uptake and conjugate bilirubin is functional; however, the removal of conjugated bilirubin from the liver cell and the excretion into the bile are defective.
This results in accumulation of conjugated and, to some extent, unconjugated bilirubin in the blood, leading to hyperbilirubinemia and bilirubinuria.
DubinJohnson syndrome
______ is a condition that is obstructive in nature, so much of the conjugated bilirubin circulates bound to albumin.
This type of bilirubin (conjugated bilirubin bound to albumin) is referred to as_____.
Dubin-Johnson
delta bilirubin
reacts as conjugated bilirubin in the laboratory method to measure conjugated or direct bilirubin.
delta bilirubin
A distinguishing feature of_______ syndrome is the appearance of______ (thought to be pigmented lysosomes) on a liver biopsy sample.
have a normal life expectancy, so no treatment is necessary.
Dubin-Johnson
dark-stained granules
T or F
the defect causing Rotor’s syndrome is not known
True
Physiologic jaundice of the newborn is a result of a deficiency in the enzyme_____, one of the last liver functions to be activated in prenatal life since bilirubin processing is handled by the mother of the fetus.
Premature infants may be born without ____, the enzyme responsible for bilirubin conjugation.
UDPGT
UDPGT deficiency results in the rapid buildup of unconjugated bilirubin, which can be life threatening.
When unconjugated bilirubin builds up in the neonate, it cannot be processed and it is deposited in the nuclei of brain and degenerate nerve cells, causing______.
kernicterus
Infants with this type of jaundice are usually treated with_____ to destroy the bilirubin as it passes through the capillaries of the skin.
It lowers serum bilirubin levels by using____ or ____ lights to transform bilirubin into watersoluble isomers that can be eliminated without conjugation in the liver.
During this process, the baby is undressed so that as much of the skin as possible is exposed to the light, his/her eyes are covered to protect the nerve layer at the back of the eye (retina) from the bright light, and the bilirubin levels are measured at least once a day.
phototherapy
halogen or fluorescent
results from biliary obstructive disease, usually from physical obstructions (gallstones or tumors) that prevent the flow of conjugated bilirubin into the bile canaliculi.
Posthepatic jaundice
the liver cell itself is functioning, bilirubin is effectively conjugated; however, it is unable to be properly excreted from the liver.
Since bile is not being brought to the intestines, stool loses its source of normal pigmentation and becomes clay-colored.
Post hepatic jaundice
